Barcoded multiple displacement amplification for high coverage sequencing in spatial genomics

Jinhyun Kim, Sungsik Kim, Huiran Yeom, Seo Woo Song, Kyoungseob Shin, Sangwook Bae, Han Suk Ryu, Ji Young Kim, Ahyoun Choi, Sumin Lee, Taehoon Ryu, Yeongjae Choi, Hamin Kim, Okju Kim, Yushin Jung, Namphil Kim, Wonshik Han, Han-Byoel Lee (), Amos C. Lee () and Sunghoon Kwon ()
Additional contact information
Jinhyun Kim: Seoul National University
Sungsik Kim: Seoul National University
Huiran Yeom: The University of Suwon
Seo Woo Song: Children’s Heart Center, Stanford University
Kyoungseob Shin: Seoul National University
Sangwook Bae: Harvard Medical School
Han Suk Ryu: Seoul National University
Ji Young Kim: Seoul National University Hospital
Ahyoun Choi: Seoul National University
Sumin Lee: Seoul National University
Taehoon Ryu: ATG Lifetech Inc.
Yeongjae Choi: Gwangju Institute of Science and Technology (GIST)
Hamin Kim: Seoul National University
Okju Kim: ATG Lifetech Inc.
Yushin Jung: ATG Lifetech Inc.
Namphil Kim: Seoul National University
Wonshik Han: Seoul National University
Han-Byoel Lee: Seoul National University
Amos C. Lee: Seoul National University
Sunghoon Kwon: Seoul National University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Determining mutational landscapes in a spatial context is essential for understanding genetically heterogeneous cell microniches. Current approaches, such as Multiple Displacement Amplification (MDA), offer high genome coverage but limited multiplexing, which hinders large-scale spatial genomic studies. Here, we introduce barcoded MDA (bMDA), a technique that achieves high-coverage genomic analysis of low-input DNA while enhancing the multiplexing capabilities. By incorporating cell barcodes during MDA, bMDA streamlines library preparation in one pot, thereby overcoming a key bottleneck in spatial genomics. We apply bMDA to the integrative spatial analysis of triple-negative breast cancer tissues by examining copy number alterations, single nucleotide variations, structural variations, and kataegis signatures for each spatial microniche. This enables the assessment of subclonal evolutionary relationships within a spatial context. Therefore, bMDA has emerged as a scalable technology with the potential to advance the field of spatial genomics significantly.

Date: 2023
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DOI: 10.1038/s41467-023-41019-w

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